Neuroblastoma is a rare developmental tumour of young children accounting for a disproportionally high proportion of paediatric cancer deaths. Increasing insights into neuroblastoma genetics and biology led to the identification of the MDM2 antagonist idasanutlin as a promising therapeutic strategy. In this thesis, we investigated two key aspects that could facilitate the clinical implementation of idasanutlin for the treatment of neuroblastoma patients. First, we identified the BCL2 inhibitor venetoclax as a synergistic drug partner of idasanutlin using both in vitro and in vivo model systems of neuroblastoma. Second, we discovered circulating miRNAs that dynamically respond to p53 activation in mice carrying human neuroblastoma xenografts; opening up possibilities for non-invasive treatment monitoring.

(BELG J MED ONCOL 2018;12(1):26–28)